The growth of the aging population in the United States has led to calls for increased research focused on enhancing end-of-life (EOL) care for dying persons and their family members. A 2004 National Institutes of Health (NIH) State of the Science Conference on Improving EOL Care noted that the current state of knowledge is in its infancy and identified the need for more research on conceptual models, infrastructure, methodological issues, treatment, outcomes, and policy. The Conference recommendations included a call for research on ethical issues, recognizing that research conducted at the EOL raises complex ethical questions related to consent, capacity, proxy decision-making, and the evaluation of risks and benefits that may inhibit the conduct of this vital research and serve as a barrier to the advancement of the science in this area. Questions about how to best balance the pressing need for research with the rights of the dying and their families reflect ethical concerns that trouble investigators, institutional review boards (IRBs), and scientific reviewers alike. Yet, empirical data are lacking regarding best practices for managing these issues to assist in the development of research that balances ethical considerations with the advancement of science. In order to identify best practices for the conduct of EOL research, the aims of this proposal are to: 1) Compare what investigators, institutional review boards, and scientific reviewers identify as ethical concerns in end-of-life research;2) Identify approaches used by investigators, institutional review boards, and scientific reviewers to resolve ethical concerns in end-of-life research;and 3) Describe the impact of ethical concerns identified by investigators, institutional review boards, and scientific reviewers on the conduct of end-of-life research. End-of-life research will be identified from the web and current literature. Principal investigators of 40-50 studies will be asked to share study documents including grant proposals, scientific reviews, and IRB communications. Qualitative telephone interviews will be conducted with case principal investigators to clarify questions raised by the documents and the impact of ethical concerns on their research. This study is innovative because it uses an exploratory case study design capitalizing on primary data sources to obtain information about the perspectives of key stakeholders responsible for the ethical conduct of research. Study findings will serve to enhance and promote the ethical conduct of human subjects research at the EOL to improve care of the dying and their family members. PUBLIC HEALTH RELEVANCE: There is a pressing need for increased research on end-of-life care, but ethical concerns have been identified as a possible impediment to the development of this field. The proposed study is designed to assess the perspectives of key stakeholders responsible for the review, approval, and ethical conduct of research to better understand how ethical concerns shape the development of end-of-life studies. At the completion of this study, data will be available to: (a) describe the characteristics of ethical concerns that arise in the conduct of end-of-life research;(b) identify approaches to resolve ethical concerns for use in the design and review of end-of-life research;and (c) understand the impact of ethical concerns on the conduct of end-of-life research.